1. Field of the Invention
The present invention relates to a device and method for concentrating blood fraction. In particular, the device and method are useful for preparing a plasma concentrate for use in a coagulum-based wound sealant.
2. Description of the Related Art
Wound sealants are compositions that mimic the body""s natural repair processes when applied to damaged tissues and vessels. In particular, wound sealants are designed to prevent persistent fluid loss from or into a wound, which can increase patient discomfort and morbidity, prolong recovery, and compromise or prevent an otherwise successful surgical outcome.
The problem of fluid leakage is particularly severe in highly vascularized tissues, such as kidney, liver, spleen and cancellous bone, which continue to bleed even after electrocautery. Arterial vascular grafts often leak at sites of anastomosis, along suture lines, and even through the grafts. Dural wounds are extremely difficult to repair, with a 30 percent failure rate for some of the best currently available procedures. Resection of lung tissue often results in persistent air leaks, which significantly prolong recovery. Moreover, such problems are often exacerbated in patients suffering from diabetes or other disease processes that impair normal wound healing.
The use of fibrinogen-based wound sealants has received widespread attention as a solution to the problem of fluid leakage. Such wound sealants are formed by using a fibrinogen activator, such as thrombin, to cleave fibrinogen to form fibrin, followed by formation of a coagulum by fibrin-fibrin crosslinking. Fibrin molecules also form crosslinks with collagen, a principle constituent of most tissues. These fibrin-collagen crosslinks promote adherence of the coagulum to the tissue to be sealed.
This approach offers a number of advantages. First, the rate of coagulum formation can be adjusted to suit the needs of a particular application by adjusting the concentration of fibrinogen activator in the mixture. Second, fibrinogen-based wound sealants are predominantly physiologic in origin, and therefore normal fibrinolytic processes remove the coagulum, typically within two to three weeks, leaving minimal scarring. If desirable, coagulum breakdown can be slowed by the addition of antifibrinolytics such as xcex5-amino caproic acid, tranexamic acid, or aprotinin. Finally, other chemical agents, such as antibiotics or anticancer drugs, can be added to the fibrinogen and/or fibrinogen activator solutions before mixing to provide sustained release of the agent at the wound site.
Fibrin for these wound sealants is typically obtained from blood or a blood fraction, such as plasma. One type of wound sealant which depends on fibrinogen and other associated plasma proteins as the procoagulant constituents has been termed xe2x80x9cfibrin gluexe2x80x9d. Wound sealants of this type, derived from pooled blood, are widely available in Europe. However, the sale of such pooled blood-derived fibrin glues is banned in the United States because of the risk of disease transmission. Recent efforts aimed at avoiding the problems of disease transmission and immunological complications associated with the use of donor materials, have focused on the possibility of using a patient""s own plasma as a fibrinogen source. However, the strength and adhesiveness of fibrinogen-based wound sealants are directly related to the fibrinogen concentration. Typical plasma fibrinogen values, which range from 2.0 to 4.5 for healthy patients, are known to provide too low a fibrinogen concentration to form a suitable fibrinogen-based wound sealant. Furthermore, disease processes, drugs, and treatment regimens can cause plasma fibrinogen levels to drop significantly lower than normal values.
Consequently, various methods of concentrating autologous fibrinogen-containing solutions have been explored. Cryoprecipitation methods are effective, but entail complex processing steps and require expensive equipment and highly trained personnel. Furthermore, preparation time ranges from hours to days, which rules out the use of cryoprecipitation methods when unexpected, acute treatment is required. Platelet-rich plasma has been used to provide clotting factors present in platelets. This use has frequently been unsuccessful because the fibrinogen level of platelet-rich plasma remains low. Other methods are based on admixture of foreign materials, such as polyethylene glycol or ammonium sulfate. These methods also suffer from excessive complexity and can expose the patient to undesirable contaminants.
A reliable method of preparing a plasma concentrate containing fibrinogen that is rapid, simple, and economical would facilitate the preparation of coagulum-based wound sealants. In particular, the ability to rapidly prepare autologous wound sealants would make the benefits of wound sealants available to patients who require acute treatment.
The present invention provides a device for concentrating a blood fraction. The device includes an ultrafiltration unit having first and second openings and an outlet adapted to connect to a vacuum source. The first opening is connected by a first valve to a fluid delivery system for delivering the blood fraction to be concentrated into the ultrafiltration unit. The second opening is connected by a second valve to a purge fluid delivery system for expelling concentrate from the ultrafiltration unit. In one embodiment, the device accommodates multiple cycles of concentration.
A blood fraction concentration method is also provided. One embodiment of the method provides single-cycle concentration, while another embodiment facilitates multi-cycle processing. The device and method of the present invention are particularly useful for preparing a plasma concentrate suitable for use in a coagulum-based wound sealant.